A Phase 2 interventional study of transcranial magnetic stimulation in Depressive Disorder, Major, Depression and Mood Disorders, sponsored by Brigham and Women's Hospital. Completed at 1 site in United States. Open to participants aged 22 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-08-25.
Sponsored by Brigham and Women's Hospital · Phase 2, Interventional, and Treatment
The goal of this clinical trial is to estimate the importance of neuroimaging in accelerated intermittent theta burst stimulation (aiTBS) for depression. Participants will receive aiTBS treatment, but they will not know if their treatment spot was found with neuroimaging or head measurements.
Techniques for modulating human brain networks are rapidly evolving. One of the most exciting new developments is accelerated intermittent theta burst stimulation (aiTBS), a transcranial magnetic stimulation (TMS) protocol that involves multiple daily treatments rather than gold standard once daily treatment. A specific accelerated iTBS protocol called Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) was cleared by the FDA in September 2022 based on two pilot studies in which patients with treatment-resistant depression rapidly and robustly improved with SAINT. Many of these patients had been depressed for decades and had not improved with conventional TMS or electroconvulsive therapy. Despite these promising results, two issues may limit SAINT scalability: 1) SAINT has only been tested at a single site in a small number of patients, 2) SAINT has never been tested without individualized resting state functional connectivity (rsfc) targeting, which is not widely available or covered by insurance. In this pilot trial, patients with treatment-resistant depression (n=40) will be randomized to one of two active treatment arms: 1) Real aiTBS with real individualized rsfc targeting, or 2) Real aiTBS with sham individualized rsfc targeting (i.e. conventional TMS targeting based on scalp landmarks). All patients will receive active stimulation, which will facilitate enrollment and reduce ethical concerns about placebo treatment in a vulnerable population when there is existing evidence of treatment efficacy. Patients and clinicians will be blind to group assignment, and blind integrity will be assessed. All patients will undergo MRI scans immediately before treatment and at one month follow up, which aligns with our clinical outcome measures.
2,741 studies on the registry are indexed under Depressive Disorder, Major; 559 are open to participants now.
This study's enrollment of 40 is below the median of 80 across 2,283 interventional studies indexed under Depressive Disorder, Major.
Browse Depressive Disorder, Major studies →Brigham and Women's Hospital is the lead sponsor of 1,236 studies on the registry; 224 are open to participants now.
Of its 116 completed or terminated interventional studies of FDA-regulated products, 64 (55%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Participants in this group will receive aiTBS with neuronavigation to a treatment target identified with individualized resting state functional connectivity.
Procedure: transcranial magnetic stimulation
Participants in this group will receive aiTBS with neuronavigation to a treatment target identified with head measurements (i.e., Beam F3)
Procedure: transcranial magnetic stimulation
Transcranial magnetic stimulation (TMS) is a focal, non-invasive form of brain stimulation that has FDA clearance for depression. In this study, a form of TMS called accelerated intermittent theta burst stimulation will be administered under the supervision of a physician with TMS expertise. This protocol will be modeled after the FDA cleared Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) protocol, but the patented SAINT rsfc targeting algorithm will not be used for either arm.
Also known as: TMS, theta burst stimulation, accelerated intermittent theta burst stimulation, aiTBS
Montgomery-Åsberg Depression Rating Scale (MADRS)
Depression severity rating scale (0-60, higher numbers indicate higher severity). The primary outcome measure was the baseline-adjusted MADRS score one month after treatment. The primary analysis of this primary outcome measure was the effect size of connectivity-based targeting.
Time frame: Baseline, one month after treatment
Beck Depression Inventory (BDI)
Depression severity rating scales (0-63, higher numbers indicate higher severity)
Time frame: Screening, Day 5 of Treatment, 1 Week Post Treatment, & 1 Month Post Treatment
Beck Anxiety Inventory (BAI)
Anxiety severity rating scale (0-63, higher numbers indicate higher severity)
Time frame: Screening, Day 5 of Treatment, 1 Week Post Treatment, & 1 Month Post Treatment
Montgomery-Åsberg Depression Rating Scale (MADRS)
Depression severity rating scale (0-60, higher numbers indicate higher severity). The primary analysis of the primary outcome will be the effect size of imaging-guided accelerated TMS relative to scalp-targeted TMS. In other words, the "number needed to scan." This outcome has not changed since the original grant application for this study and the data remain blinded at the time of this clarification. Actual group differences will be explored in a secondary analysis of this primary outcome measure.
Time frame: Baseline & 1 Month Post Treatment
Change in Resting State Functional Connectivity in the Depression Network
Blood oxygen level-dependent (BOLD) signal.
Time frame: Baseline, one month after treatment
Temperament and Character Inventory, Revised 140-item
Psychobiologically-based personality inventory which measures seven personality dimensions (harm avoidance, novelty seeking, reward dependence, persistence, self-directedness, cooperativeness, and persistence). For each dimension, this yields a scaled T-score (mean score of 50 with standard deviation of 10). This is an overall estimate of personality traits, and there are no "better" or "worse" traits.
Time frame: Baseline, one month after treatment
Emotional Conflict Resolution Task
Computer task measuring accuracy and reaction time
Time frame: Baseline, one month after treatment
Learning, Multi-Source Interference Task (MSIT)
Computer task measuring accuracy and reaction time
Time frame: Baseline, one month after treatment
Penn Emotion Recognition Task (ER-40)
Computer task measuring accuracy and reaction time
Time frame: Baseline, one month after treatment
Death Suicide IAT (DSIAT)
Computer task measuring reaction time
Time frame: Baseline, one month after treatment
Recruitment ran July 2023-March 2025. Recruitment sources included Rally, Mass General Brigham outpatient clinics/healthcare providers, and clinicaltrials.gov. Additionally, flyers were posted around the greater Mass General Brigham area.
| Milestone | Connectivity-based Targeting | Scalp-based Targeting |
|---|---|---|
| Started | 20 | 20 |
| Completed | 20 | 20 |
| Not completed | 0 | 0 |
Depression severity rating scale (0-60, higher numbers indicate higher severity). The primary outcome measure was the baseline-adjusted MADRS score one month after treatment. The primary analysis of this primary outcome measure was the effect size of connectivity-based targeting.
| Scores on scale | Connectivity-based Targeting | Scalp-based Targeting |
|---|---|---|
| Baseline | 35 (28 to 38.25) | 31 (26 to 33.25) |
| 1 Month | 6 (1.5 to 12.5) | 11 (4 to 22) |
Depression severity rating scales (0-63, higher numbers indicate higher severity)
| Scores on scale | Connectivity-based Targeting | Scalp-based Targeting |
|---|---|---|
| Screening | 37 (26.00 to 44.50) | 28.50 (23.00 to 34.50) |
| Day 5 of Treatment | 11.50 (7.00 to 31.50) | 13.50 (10.00 to 17.00) |
| 1 Week Post Treatment | 8 (1.50 to 25.50) | 10 (6.00 to 18.00) |
| 1 Month Post Treatment | 10 (2.00 to 22.00) | 10.00 (5.00 to 17.50) |
Anxiety severity rating scale (0-63, higher numbers indicate higher severity)
| Scores on scale | Connectivity-based Targeting | Scalp-based Targeting |
|---|---|---|
| Screening | 15 (5.50 to 19.00) | 19 (12.50 to 31.00) |
| Day 5 of Treatment | 0 (0.00 to 3.25) | 3 (2.00 to 4.00) |
| 1 Week Post Treatment | 0 (0.00 to 4.00) | 2.50 (2.00 to 6.00) |
| 1 Month Post Treatment | 1 (0.00 to 5.50) | 3 (2.00 to 5.00) |
Depression severity rating scale (0-60, higher numbers indicate higher severity). The primary analysis of the primary outcome will be the effect size of imaging-guided accelerated TMS relative to scalp-targeted TMS. In other words, the "number needed to scan." This outcome has not changed since the original grant application for this study and the data remain blinded at the time of this clarification. Actual group differences will be explored in a secondary analysis of this primary outcome measure.
| Scores on scale | Connectivity-based Targeting | Scalp-based Targeting |
|---|---|---|
| Baseline | 36 (28 to 38.25) | 31 (26 to 33.25) |
| 1 Month Post Treatment | 6 (1.5 to 12.5) | 11 (2 to 22) |
Blood oxygen level-dependent (BOLD) signal.
Results for this outcome have not been posted.
Psychobiologically-based personality inventory which measures seven personality dimensions (harm avoidance, novelty seeking, reward dependence, persistence, self-directedness, cooperativeness, and persistence). For each dimension, this yields a scaled T-score (mean score of 50 with standard deviation of 10). This is an overall estimate of personality traits, and there are no "better" or "worse" traits.
Results for this outcome have not been posted.
Computer task measuring accuracy and reaction time
No measurements were reported for this outcome.
Computer task measuring accuracy and reaction time
No measurements were reported for this outcome.
Computer task measuring accuracy and reaction time
No measurements were reported for this outcome.
Computer task measuring reaction time
No measurements were reported for this outcome.
Collected over Day 1 to day 5 of treatment. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Connectivity-based Targeting | 0/20 (0%) | 0/20 (0%) | 16/20 (80%) |
| Scalp-based Targeting | 0/20 (0%) | 0/20 (0%) | 14/20 (70%) |
| Event | Connectivity-based Targeting | Scalp-based Targeting |
|---|---|---|
| Scalp discomfortGeneral disorders | 9/20 | 13/20 |
| HeadacheNervous system disorders | 5/20 | 11/20 |
| Worsening symptoms of anxietyPsychiatric disorders | 6/20 | 2/20 |
| Face twitching/tinglingNervous system disorders | 5/20 | 5/20 |
| Tinnitus (ringing in the ears)Ear and labyrinth disorders | 4/20 | 2/20 |
| Worsening symptoms of depressionPsychiatric disorders | 3/20 | 2/20 |
| Suicidal IdeationPsychiatric disorders | 1/20 | 1/20 |
| Age, Customized(Years) | Connectivity-based Targeting | Scalp-based Targeting | Total |
|---|---|---|---|
| Age (Mean, SD) | 42.95 ± 14.24 | 48.45 ± 15.95 | 45.70 ± 15.18 |
| Sex/Gender, Customized(Participants) | Connectivity-based Targeting | Scalp-based Targeting | Total |
|---|---|---|---|
| Female | 12 | 10 | 22 |
| Male | 8 | 10 | 18 |
| Race/Ethnicity, Customized(Participants) | Connectivity-based Targeting | Scalp-based Targeting | Total |
|---|---|---|---|
| White | 13 | 16 | 29 |
| Black or African American | 1 | 0 | 1 |
| Asian | 3 | 2 | 5 |
| Multiracial | 3 | 1 | 4 |
| Unknown/not reported | 0 | 1 | 1 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Undecided — De-identified survey response data and/or neuroimaging data may be shared with collaborators for further analysis.
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